Pulmonary arterial hypertension (PAH) is a condition in which the pressure in the lung circulation increases, eventually causing heart failure and death. The etiology of PAH is complex, but aberrant proliferation of the pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) is thought to play an important role in its pathogenesis. Recent identification of a key signaling paradigm in PAECs involving apelin demonstrated the importance of crosstalk among molecules in maintenance of pulmonary vascular homeostasis. The activity of the transcription factor myocyte enhancer factor 2 (MEF2) was also found to be significantly decreased in PAH PAECs. Whether this is the primary event in the development of PAH or part of a downstream cascade remains unknown, but in either case it is an important factor in the progressive vasoconstriction and vascular proliferation that characterize the disease.
Therefore, a need exists for restoring normal function within these cells to reduce or improve pulmonary arterial hypertension.